Introduction Motivation in medical students is positively associated with learning strategies. However, the evidence of a direct relationship between motivation and performance is vague. The objective of this study is to determine if the motivation that pushed students to choose the medical career is associated with their academic performance during their university years. Methods The study was conducted in 4,290 medical students from 10 countries in Latin America. The “Attribution Scale of General Achievement Motivation” was used to evaluate their general performance. The “Medical motivation Scale” test was used to measure social, altruist, economic, and prestige motivators. For statistical analyses, frequencies and percentages were described, and generalized linear models were used to establish statistical associations. Results Fifty percent of the students surveyed were females and the mean student age was 21 years old. This study showed that male students had a higher social/altruist motivation (PR:1.11,95%CI: 1.03–1.18; p<0,01) than females. Those who had familial pressure had a lower social/altruist motivation (PR:0.17,95%CI:0.08–0.36; p<0,001). The positive vocational test was associated with a higher social/altruist motivation (PR:1.85,95%CI:1.03–3.30; p<0,05). Moreover, good grades at school were related with a higher economical/prestige motivation (PR:1.39,95%CI:1.05–1.83; p<0,05), but lower social/altruist motivation (PR:0.85,95%CI:0.74–0.98; p<0,05) and academic performance (PR:0.63,95%CI:0.50–0.79; p<0,001). We found a higher frequency in the general motivation was associated to a lowest social/altruist motivation (PR: 0.57; CI95%: 0.46–0.70; p<0.001), and that it increased according to the year of study (PR: 1.15; CI95%: 1.03–1.28; p:0.013) and was higher when pressure by the family was present (PR: 1.36; CI95%: 1.17–1.59; p<0.001). Conclusion This study indicated that male medical students and having a positive vocational test were associated with a higher social/altruist motivation. Conversely, those who had familial pressure and good grades at school had a lower social/altruist motivation. Is necessary to conduct further studies that assess other factors related to motivation as demographics, personality, and learning styles.